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Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: a protocol for a systematic review and network meta-analysis
  1. Kyeore Bae1,
  2. Si Yeon Song2
  1. 1Department of Integrative Medicine, Center for Immunity and Pain, Kwanghye Hospital, Seoul, Republic of Korea
  2. 2East-West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon, Republic of Korea
  1. Correspondence to Dr Kyeore Bae; kyeorebae{at}


Introduction Aromatase inhibitor-induced arthralgia (AIA) is a major adverse event of aromatase inhibitors (AIs) and leads to premature discontinuation of AI therapy in breast cancer patients. The objective of this protocol for a systematic review and network meta-analysis (NMA) is to provide the methodology to compare the change in pain intensity between different AIA treatments and demonstrate the rank probabilities for different treatments by combining all available direct and indirect evidence.

Methods and analysis PubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE, Web of Science and will be searched to identify publications in English from inception to November 2019. We will include randomised controlled trials (RCTs) assessing the effects of different treatments for AIA in postmenopausal women with stage 0–III hormone receptor-positive breast cancer. The primary endpoints will be the change in patient-reported pain intensity from baseline to post-treatment. The number of adverse events will be presented as a secondary outcome.

Both pairwise meta-analysis and NMA with the Frequentist approach will be conducted. We will demonstrate summary estimates with forest plots in meta-analysis and direct and mixed evidence with a ranking of the treatments as the P-score in NMA. The revised Cochrane risk-of-bias tool for randomised trials will be used to assess the methodological quality within individual RCTs. The quality of evidence will be assessed.

Ethics and dissemination As this review does not involve individual patients, ethical approval is not required. The results of this systematic review and NMA will be published in a peer-reviewed journal. This review will provide valuable information on AIA therapeutic options for clinicians, health practitioners and breast cancer survivors.

PROSPERO registration number CRD42019136967.

  • aromatase inhibitor
  • arthralgia
  • breast tumours
  • pain management
  • network meta-analysis

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • KB and SYS are joint first authors.

  • KB and SYS contributed equally.

  • Contributors KB contributed to conceptualisation, study design and funding acquisition; supervised the research. SYS contributed to investigation and visualisation of data. KB and SYS designed the risk of bias approach and statistical analysis plan; wrote original draft. Both the authors read the manuscript and approved the publication of the protocol. The research has not been conducted.

  • Funding This research is supported by a grant of the Research Supporting Programme, MIMICUS Inc. (MIMIC2019-RS07). The funders had no role in development of the protocol, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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